The administration of a deuterium-labeled drug together with a prodrug made it possible to determine the bioconversion rate of the prodrug into the patent compound accurately in dogs. Deuterated indomethacins were prepared from acetaldehyde p-methoxyphenylhydrazone in 4 steps. Indomethacin in blood plasma was derivatized into the hexafluoroisopropyl ester and determined by means of selected ion monitoring employing indomethacin-d9 as an internal standard. When a single dose of indomethacin or oxametacin was orally given to dogs, the time courses of plasma level of indomethacin were remarkably different form one another. The bioconversion rate of oxametacin into indomethacin could apparently not be directly estimated form the area under the drug concentration-time curve (AUC) value. When a mixture of indomethacin-d4 and oxametacin was administered to 3 dogs, the ratios of the AUC value of the non-labeled indomethacin derived from oxametacin to that of the labeled indomethacin in the dogs were almost equal. This approach was also applicable to the estimation of acemetacin. The bioavilabilities of oxametacin and acemetacin can evidently be fairly accurately evaluated with a small number of animals by the combined use of labeled indomethacin and selected ion monitoring.